Joris van Dongen

163 The power of fat and ASCs for scar treatment: a review Scar histology has been investigated in two studies using irradiation skin damage models in rodents 50,51 (Table 2a). Skin fibrosis after radiation in general is a clinical relevant problem, which can easily be reproduced in rodents.After radiation, dermatitis develops, which eventually gives rise to fibrotic skin characterized by epidermal thickening and irregular deposition of collagen in the dermis. Also, compared to normal skin, irradiated skin areas have an increased vessel density. In two studies in mice, it has been shown that treatment with lipofilling can reduce all these hallmark features of radiation-damaged skin 50,51 . Decrease in SMAD3 protein levels, a key protein in the pro-fibrotic pathway TGF- β /Smad signal transduction pathway, partly explains the mechanism of scar improvement 50 . In a slightly different model in mice with full thickness burn wounds, it has been shown that lipofilling leads to better scar appearance by increasing pro-angiogenic factors VEGF and stromal cell-derived factor 1 (SDF-1) and decreasing pro-fibrotic factor TGF- β 1 52 . Reduction of neuropathic pain has been reported in two studies of Huang and co- workers 53,54 Ttable 2b). Allodynia, painful perception of a normally non-painful stimulus, after burnwound injurywas tested in rats bymeans of behavioral testing.After burn injury, lipofilling reduced burn induced allodynia. On the one hand, lipofilling reduces skin fibrosis and scarring after burn injury 53,54 and lowers expression of pro- inflammatory mediators in the skin 54 . On the other hand, lipofilling induces changes in the spinal cord as well decreases microglial activation and by lessens activation of the pro-inflammatory NFkB signal transduction pathway in spinal cord cells 54 . It can be concluded that lipofilling in rodent models for skin injury and fibrosis, reduces adverse fibrotic changes. This appears to be mediated by factors from the lipograft that can inhibit activation of both fibrotic and inflammatory signal transduction pathways. All changes caused by lipofilling in a dermal scar have been drawn schematically in Figure 1.